Semaglutide (GLP-1) (3mg / 5mg / 10mg)

Semaglutide (GLP-1) Peptide

Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) analog. GLP-1 peptide is an endogenous peptide hormone containing 30-31 amino acids. Ongoing research suggests that the primary implications of this compound are increased insulin production, reduced glycemic levels, and conservation of pancreatic beta cells by stimulating insulin gene transcription. Additionally, the compound appears to delay gastric emptying, leading to appetite suppression and reduced caloric intake. Semaglutide, as a GLP-1 receptor agonist, may potentially lower gastric motility and glucose, reduce appetite, and induce weight loss.⁽¹⁾ The peptide may exert its potential via various pathways, including:^(2,3,4)

• Possibly binding with the GLP-1 receptors in pancreatic tissues, promoting glucose-dependent insulin release.
• Possibly suppressing the release of glucagon and inhibiting the hepatic synthesis of glucose.
• Possibly via pancreatic beta cell functioning, improving the proinsulin-to-insulin ratio
• Possibly delaying gastric motility, interacting with hunger-regulating centers and reducing appetite.

Chemical Makeup⁽⁵⁾

Molecular Formula: C₁₈₇H₂₉₁N₄₅O₅₉
Molecular Weight: 4114 g/mol
Other Titles: Glucagon-like peptide-1 (GLP-1)

Research and Clinical Studies

Semaglutide Peptide and Pancreatic Beta Cells Activation

Semaglutide is hypothesized to interact with the GLP-1 receptors in the pancreas, potentially stimulating insulin production in pancreatic beta cells and possibly suppressing glucagon production by pancreatic alpha cells.⁽⁶⁾ Overall, this is expected to result in improved glucose control. The GLP-1 receptors are G-protein-coupled receptors (GPCRs). Should Semaglutide bind to these receptors, it may cause a change in their structure, potentially activating G-proteins inside the cell. This activation may lead to the exchange of GDP for GTP on the G-protein, triggering a signaling pathway that involves the enzyme adenylyl cyclase. Adenylyl cyclase may then convert ATP to cyclic AMP (cAMP), which in turn may activate protein kinase A (PKA). PKA might phosphorylate various proteins, leading to several cellular actions. Semaglutide might also activate the GLP-1 receptor-mediated phosphoinositide 3-kinase (PI3K) pathway. This pathway could produce phosphatidylinositol 3,4,5-trisphosphate (PIP3), activating protein kinase B (Akt). Akt regulates processes such as glucose uptake, glycogen synthesis, and cell survival. According to the research teams exploring this action, the impact of Semaglutide appears to act in a glucose-dependent manner. Thus, the peptide is posited to improve glucose control without posing a risk for hypoglycemia.

Semaglutide Peptide and Pancreatic Beta Cells Protection

Additionally, Semaglutide may recruit beta-arrestins to the GLP-1 receptor. Beta-arrestins might help regulate receptor signaling and internalization.⁽⁷⁾ When beta-arrestins bind to the receptor, they might facilitate receptor desensitization (reducing responsiveness to continuous stimulation) and internalization (removing the receptor from the cell surface). This internalization might involve clathrin-coated pits forming vesicles transporting the receptor to be degraded or recycled. Beta-arrestins might also initiate alternative signaling pathways, such as the MAPK pathway, which is considered to influence cell growth, differentiation, and survival. Indeed, research suggests that pancreatic beta cells may exert improved survival when exposed to Semaglutide. An experiment was conducted on non-obese and diabetic mice models presented with a GLP-1 agonist similar to Semaglutide, in combination with lisofylline (a compound that suppresses the autoimmune ability). ⁽⁸⁾ The results suggested that the peptide might promote the growth of pancreatic beta cells and prevent cellular apoptosis. In addition to possibly protecting the pancreatic beta cells, The GLP-1 agonist peptide was suggested by the researchers to help maintain the optimal glucose levels in the animal 145 days after peptide exposure was removed. Overall, the researchers concluded that the experiment “was associated with improved beta-cell metabolism and insulin secretion, while reducing beta-cell apoptosis.”

Semaglutide Peptide and Appetite

GLP-1 receptor agonists such as Semaglutide may possibly delay gastric acid motility, contributing to satiation and reducing appetite.⁽¹⁾ Studies have posited that it appears to slow gastric emptying, potentially by up to 38%, within the initial hours following a meal, which may contribute to early satiety and reduced appetite. Further, research has suggested that when presented in the brain, these peptides might decrease the drive to consume food and prevent food intake.⁽⁹⁾ More specifically, the data implies a potential link between the activation of GLP-1 receptors in the reward-related brain areas and the modulation of appetite observed with Semaglutide.⁽¹⁰⁾ The proposed mechanism suggests that GLP-1 receptor agonists, such as Semaglutide, may engage with specific neurons within the arcuate nucleus of the hypothalamus. This interaction between GLP-1 receptor agonists and hypothalamic neurons is underpinned by a complex neurochemical pathway. The arcuate nucleus, where these neurons reside, is a pivotal hub in the neuroendocrine system, integrating peripheral signals related to energy status and modifying behavioral and physiological responses accordingly. These specific neurons are believed to play a critical role in the control of appetite and hunger. They are thought to express proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). The activation of these POMC/CART neurons by Semaglutide may potentially lead to increased feelings of fullness and indirectly suppress the release of neuropeptide Y (NPY) and agouti-related peptide (AgRP), which are peptides implicated in the promotion of hunger. Additionally, there is a hypothesis that during periods of weight loss, GLP-1 receptor agonists like Semaglutide might help counteract the reduction in free leptin levels and possibly raise levels of peptide YY (PYY) 3-36.⁽¹¹⁾ Overall, studies suggest that the appetite suppression induced by Semaglutide may be significant. For example, one study posits that Semaglutide may facilitate a notable reduction of about 35% in average energy consumption during meals where food is freely available, when compared to a placebo (1736kJ vs. 2676kJ).⁽¹²⁾

Semaglutide and Neurological Potential

The GLP-1 receptor, GLP-1R, is considered vital in facilitating certain cognitive processes. GLP-1 and GLP-1R are expressed in brain cells. When GLP-1R is deficient in the brain, it may cause seizures, impaired learning abilities, and neuronal injury. When bound to these receptors, it might improve cognitive and learning abilities. As per Mathew J During et al., “Systemic [exposure] of GLP-1 receptor agonists in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons..” ⁽¹³⁾ These results might indicate the potential of GLP-1 peptides like Semaglutide within neurological research. Further, studies specifically focused on Semaglutide suggest that the peptide potentially influences neuroprotection through several mechanisms, notably in the brain, where it might reduce neuroinflammation, apoptosis, and oxidative stress. A scientific review suggests that Semaglutide's protective roles may be mediated through its interaction with GLP-1 receptors widely distributed in the central nervous system.⁽¹⁴⁾ These receptors are involved in critical pathways that regulate neuronal functionality. For instance, Semaglutide's potential to decrease beta-amyloid plaque accumulation and support neuronal precursor cell differentiation is particularly relevant in experimental Alzheimer's models. Similarly, the compound appears to exert neuroprotective actions in experimental Parkinson’s models by potentially reducing the accumulation of the protein alpha-synuclein, which is implicated in the disease’s pathology. In addition to its direct potential on neuronal cells, Semaglutide might also influence neuroinflammation through its interaction with immune cells like microglia and astrocytes. For example, it has been observed to prevent the release of pro-inflammatory cytokines from these cells, which might mitigate the inflammatory responses often seen in neurological diseases. The data from various studies suggest that Semaglutide may improve cognitive functions and reduce neurodegeneration by modulating several molecular pathways involved in cell survival, inflammation, and oxidative stress.

Semaglutide peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

Not for human consumption.

References:

1. Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide is a glucagon like peptide-1 receptor agonist with cardiovascular benefits for the management of type 2 diabetes. Rev Endocr Metab Disord. 2022 Jun;23(3):521-539. doi: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID: 34993760; PMCID: PMC8736331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8736331/
2. Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019 Apr 12;10:155. doi: 10.3389/fendo.2019.00155. PMID: 31031702; PMCID: PMC6474072. https://pubmed.ncbi.nlm.nih.gov/31031702/
3. Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, Holst AG, Annett MP, Aroda VR. Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial. Diabetes Care. 2018 Feb;41(2):258-266. doi: 10.2337/dc17-0417. Epub 2017 Dec 15. PMID: 29246950. https://pubmed.ncbi.nlm.nih.gov/29246950/
4. Christou GA, Katsiki N, Blundell J, Fruhbeck G, Kiortsis DN. Semaglutide as a promising antiobesity drug. Obes Rev. 2019 Jun;20(6):805-815. doi: 10.1111/obr.12839. Epub 2019 Feb 15. PMID: 30768766. https://pubmed.ncbi.nlm.nih.gov/30768766/
5. National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 56843331, Semaglutide.
6. Zhao, X., Wang, M., Wen, Z., Lu, Z., Cui, L., Fu, C., Xue, H., Liu, Y., & Zhang, Y. (2021). GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects. Frontiers in endocrinology, 12, 721135. https://doi.org/10.3389/fendo.2021.721135
7. Hager, M. V., Johnson, L. M., Wootten, D., Sexton, P. M., & Gellman, S. H. (2016). β-Arrestin-Biased Agonists of the GLP-1 Receptor from β-Amino Acid Residue Incorporation into GLP-1 Analogues. Journal of the American Chemical Society, 138(45), 14970–14979. https://doi.org/10.1021/jacs.6b08323
8. Yang Z, Chen M, Carter JD, Nunemaker CS, Garmey JC, Kimble SD, Nadler JL. Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes. Biochem Biophys Res Commun. 2006 Jun 9;344(3):1017-22. doi: 10.1016/j.bbrc.2006.03.177. Epub 2006 Apr 5. PMID: 16643856. https://pubmed.ncbi.nlm.nih.gov/16643856/</>
9. Blonde L, Klein EJ, Han J, Zhang B, Mac SM, Poon TH, Taylor KL, Trautmann ME, Kim DD, Kendall DM. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006 Jul;8(4):436-47. doi: 10.1111/j.1463-1326.2006.00602.x. PMID: 16776751. https://pubmed.ncbi.nlm.nih.gov/16776751/
10. van Bloemendaal, L., IJzerman, R. G., Ten Kulve, J. S., Barkhof, F., Konrad, R. J., Drent, M. L., Veltman, D. J., & Diamant, M. (2014). GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes, 63(12), 4186–4196. https://doi.org/10.2337/db14-0849
11. Ard, J., Fitch, A., Fruh, S., & Herman, L. (2021). Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists. Advances in therapy, 38(6), 2821–2839. https://doi.org/10.1007/s12325-021-01710-0
12. Friedrichsen, M., Breitschaft, A., Tadayon, S., Wizert, A., & Skovgaard, D. (2021). The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes, obesity & metabolism, 23(3), 754–762. https://doi.org/10.1111/dom.14280
13. During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. The glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. doi: 10.1038/nm919. Epub 2003 Aug 17. PMID: 12925848. https://pubmed.ncbi.nlm.nih.gov/12925848/
14. Tipa, R. O., Balan, D. G., Georgescu, M. T., Ignat, L. A., Vacaroiu, I. A., Georgescu, D. E., Raducu, L., Mihai, D. A., Chiperi, L. V., & Balcangiu-Stroescu, A. E. (2024). A Systematic Review of Semaglutide's Influence on Cognitive Function in Preclinical Animal Models and Cell-Line Studies. International journal of molecular sciences, 25(9), 4972. https://doi.org/10.3390/ijms25094972